Enrichment of c-Met+ tumorigenic stromal cells of giant cell tumor of bone and targeting by cabozantinib.

Giant cell tumor of bone (GCTB) is a very rare tumor entity, which is little examined owing to the lack of established cell lines and mouse models and the restriction of available primary cell lines. The stromal cells of GCTB have been made responsible for the aggressive growth and metastasis, emphasizing the presence of a cancer stem cell population. To identify and target such tumor-initiating cells, stromal cells were isolated from eight freshly resected GCTB tissues. Tumorigenic properties were examined by colony and spheroid formation, differentiation, migration, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, immunohistochemistry, antibody protein array, Alu in situ hybridization, FACS analysis and xenotransplantation into fertilized chicken eggs and mice. A sub-population of the neoplastic stromal cells formed spheroids and colonies, differentiated to osteoblasts, migrated to wounded regions and expressed the metastasis marker CXC-chemokine receptor type 4, indicating self-renewal, invasion and differentiation potential. Compared with adherent-growing cells, markers for pluripotency, stemness and cancer progression, including the CSC surface marker c-Met, were enhanced in spheroidal cells. This c-Met-enriched sub-population formed xenograft tumors in fertilized chicken eggs and mice. Cabozantinib, an inhibitor of c-Met in phase II trials, eliminated CSC features with a higher therapeutic effect than standard chemotherapy. This study identifies a c-Met(+) tumorigenic sub-population within stromal GCTB cells and suggests the c-Met inhibitor cabozantinib as a new therapeutic option for targeted elimination of unresectable or recurrent GCTB.

[The young resident between work and family. Status quo and approaches to a solution in orthopedics and traumatology]. / Der junge Arzt zwischen Beruf und Familie. Status quo und Lösungsansätze im Fach Orthopädie und Unfallchirurgie.

The compatibility between the family and the medical profession requires a new challenge of leadership in hospitals, politics and medical societies. The generation change in the medical profession needs the implementation of modern framework conditions in the departments of orthopedics and traumatology. Topics such as work organisation, family support and programs to assist the return to work need to be discussed and should be used as a competitive advantage. Employees of generation y need a gender-independent role model in the field of modern management methods in employee leadership.

[Promoting the next generation - what can we improve?]. / Nachwuchsförderung - Was können wir besser machen.

The surgical faculties are threatened by a shortage of junior staff which also applies to orthopedics and traumatology. This article explains which concepts the Young Forum of the German Society of Orthopedics and Traumatology (DGOU) already actively promotes to get students enthusiastic about musculoskeletal surgery and what additional efforts are needed to ensure that the measures are successful.

[Position Paper of the Youth Forum DGOU 2010 - part 2]. / Klausurtagung - Positionspapier Junges Forum der DGOU 2010 - Teil 2.

The aim of the "Youth Forum of the DGOU" during the Convention 2010 in Heidelberg was to place a statement concerning the professional politics in the field of Orthopaedic and Trauma Surgery. The Bologna Process realizes a standardization of the academic training within the European Union. For medicine this concept would raise the opportunity to opt out after three years with a bachelor degree applying for alternative occupations within the health care system. However, these alternative occupations are rarely defined and, in addition, the current structure of medical school in Germany provides the highest possible education for doctors in a direct and very well established way. Thus, reforming medical school in Germany into a Bachelor-master's system is an ambivalent approach, which considers a thorough reappraisal. There is currently no necessity for an speciality training in emergency medicine. The rapid and qualified treatment by the specific subspecialty provides a high standard of care for the patient. The high frequency exposure of the trauma and orthopaedic resident with emergency cases is an essential part of the current professional training.The "Junge Forum der DGOU" continues to understand the speciality training "Facharzt für Orthopädie und Unfallchirurgie" as the basic module of the profession. After that it should be possible to continuing subspecialty training and obtaining "spezielle Unfallchirurgie" bzw "spezielle orthopädische Chirurgie". After that further subspecialty training should be encouraged.

[Position Paper of the Youth Forum DGOU 2010 - part 1]. / Klausurtagung - Positionspapier Junges Forum der DGOU 2010 - Teil 1.

The aim of the "Youth Forum of the DGOU" during the Convention 2010 in Heidelberg was to place a statement concerning the professional politics in the field of Orthopaedic and Trauma Surgery. The emigration of young German physicians, the occupational image of the Physician Assistant and the quality of the German residency programs in Orthopaedic and Trauma Surgery we discussed as main topics. The main reason for young German physicians to go abroad is, besides better work conditions and less bureaucracy, the better structured education during residency. Therefore the "Youth Forum" generally supports the concept of the "physician assistant" as "a relief from non-physician duties rather than discussing the delegation of true physician duties". The "Youth Forum" is looking forward to collaborating on the improvement of the ongoing education of residents. In this regard, Orthopaedic and Trauma Surgery needs to become more attractive for young academics. We also support a uniform and nationwide curriculum, which guarantees a structured education to improve the theoretic, practical and academic skills of the future specialist in orthopaedic and trauma surgery. Additional surveys and interviews among the current generation of residents are needed to further specify the potential goals of such a curriculum. We would like to discuss the future of our speciality with our colleagues. Therefore different communication platforms including our website http://www.jf-dgou.de have been created.

[6 years after reformation of the specialty training reglementation--is there still room for improvement?]. / 6 Jahre nach Reform der Weiterbildungsordnung--gibt es noch Verbesserungspotenzial?

AIM: The specialty training reglementation in Germany is defined by a clear framework and aims regarding the obtainable specialty qualification. But its implementation is often difficult. The aim of the present study was to evaluate the demands of the new specialist qualification on the part of the trainers in Germany. METHOD: An e-mail questionnaire was distributed via the offices of DGU (German Society of Traumatology) and DGOOC (German Society of Orthopaedics and Orthopaedic Surgery) to 954 head physicians. Questions referred to abilities that are subject to concrete specialty training. Questions 1-3 referred to basic knowledge of the trained specialty. Questions 4 and 5 focused on self-reliant work, questions 6 and 7 touched aspects of conservative orthopaedics and multiple trauma management whereas questions 8-10 referred to the achieved surgical skills. RESULTS: 220 questionnaires were evaluated overall in a period of 6 weeks. 132 questionnaires were returned by the DGOOC and 88 by the DGU. Questions 1-3: basic knowledge regarding diagnostics and treatment of diseases and injuries of the musculoskeletal system as well as communication in adequate medical terminology were presumed by 97% and 85% respectively. 72% of the questioned trainers expected a brand new specialist to give a detailed and qualified description of an X-ray. Questions 4 and 5: 67% postulated that a brand new specialist should be capable of indicating a routine surgical intervention correctly. But only 30% expected a specialist to manage a consultation. Questions 6 and 7: the self-reliant conservative treatment of back pain patients was assumed by 60%, whereas the organisation of the medical care of multiple trauma patients is requested by 40%. Questions 8-10: referring to the surgical skills, 52% expected that one should handle the standard surgical approaches to the large extremity joints. Only 24% expected that after completing his training, a specialist can perform standard surgical procedures, which are required in the specialty training reglementation, without supervision. On the other hand they were expected to assist. CONCLUSION: Expectations of the head physicians concerning the skills of a new specialist did not match the expected skills defined in the specialty training reglementation regarding basic knowledge, self-reliant work, surgical skills as well as conservative orthopaedics and multiple trauma management. A reasonable structuring is necessary in order to implement the requested contents of the specialty training reglementation. This can only be achieved if demands on aims are compliant.